The objective of this proposal is to establish the biochemical mechanism of the cardiomyopathy previously observed to be associated with prolonged treatment with the anticancer agent, adriamycin. In this regard, we propose to study the effects of adriamycin on myocardial nucleic acid metabolism and the synthesis of specific myocardial structural and functional protein in a well documented animal model. Specifically, the synthesis rate of total RNA, mRNA, tRNA and mitochondrial RNA will be measured in myocardial cells as a function of treatment modality to determine the primary molecular level and range of drug interaction. In addition, the rate of synthesis of specific myocardial proteins representative of organelles shown to suffer severe structural damage in the cardiomyopathy will be measured to provide biochemical correlates and supportive evidence of the pathogenesis of morphologic lesions. The possible control mechanism through which drug interaction with nucleic acid metabolism results in altered protein synthesis will be probed by measuring ribosomal and RNA polymerase activity. Finally the definition and development of an assay for a myocardial-specific parameter, the myosin index, is proposed to provide an indication of the state of adriamycin-induced cardiomyopathy.